Neoadjuvant Adaptive Pazopanib With Concurrent Fixed-Dose Radiation in Localized Soft-Tissue Sarcoma

There is a critical need to improve the pathologic outcomes for patients with localized resectable soft-tissue sarcoma (LR-STS) receiving preoperative radiation therapy (RT) and surgery. We sought to determine the pathologic outcomes of patients receiving toxicity-adjusted pazopanib concurrently with fixed-dose RT.

We performed a retrospective single-institution study of patients with LR-STS receiving preoperative RT and pazopanib. Patients received pazopanib, adjusted between daily dosing of 200 and 800 mg depending on tolerance, along with a fixed dose of preoperative RT (50 Gy in 25 fractions). Outcomes included pnCR (≤5% viable tumor [VT] following resection), mPR (≤10% VT), pPR (10% to 50% VT), radiologic response, adverse events, and distant metastasis-free survival (DMFS).

Fourteen patients with LR-STS were included. Five patients (35.7%) had pnCR, 3 patients (21.4%) had mPR, and 6 patients had pPR. The median DMFS was 6 months (IQR: 19). Nine patients completed the full course of pazopanib at 800 mg with preoperative RT and recorded a pnCR rate of 44.5% (n=4) and mPR rate of 22.3% (n=2). Three patients (33.4%) recorded a pPR. Five patients received pazopanib between 200 and 600 mg with preoperative RT and had a pnCR of 20% and mPR of 20%. Median DMFS was 14 months (IQR: 24). Grade 3 treatment-related hypertension was noted in 3 patients, and 1 patient had wound dehiscence.

Concurrent administration of pazopanib with fixed-dose RT increases the likelihood of pnCR and mPR compared with historical controls. Dose adjustment of pazopanib to prevent toxicity does not affect outcomes.